Epidermal langerhans cells rapidly capture and present antigens from C-type lectin-targeting antibodies deposited in the dermis

Antigen-presenting cells can capture antigens that are deposited in the skin, including vaccines given subcutaneously. These include different dendritic cells (DCs) such as epidermal Langerhans cells (LCs), dermal DCs, and dermal langerin DCs. To evaluate access of dermal antigens to skin DCs, we used mAb to two C-type lectin endocytic receptors, DEC-205/CD205 and langerin/CD207. When applied to murine and human skin explant cultures, these mAbs were efficiently taken up by epidermal LCs. In addition, anti-DEC-205 targeted langerin CD103 and langerin CD103 mouse dermal DCs. Unexpectedly, intradermal injection of either mAb, but not isotype control, resulted in strong and rapid labeling of LCs in situ, implying that large molecules can diffuse through the basement membrane into the epidermis. Epidermal LCs targeted in vivo by ovalbumin-coupled anti-DEC-205 potently presented antigen to CD4 and CD8 T cells in vitro. However, to our surprise, LCs targeted through langerin were unable to trigger T-cell proliferation. Thus, epidermal LCs have a major function in uptake of lectin-binding antibodies under standard vaccination conditions

Corrigendum to Murine Langerin+ dermal dendritic cells prime CD8+ T cells while Langerhans ells induce cross-tolerance

[No abstract available

Analysis of a model with a common source of CP violation

We work in a model where all CP violating phenomena have a common source. CP is spontaneously broken at a large scale $V$ through the phase of a complex singlet scalar. An additional $SU(2)_L$ singlet vector-like down-type quark relates this high scale CP violation to low energy. We quantitatively analyze this model in the quark sector. We obtain the numerical values of the parameters of the Lagrangian in the quark sector for a specific ansatz of the $4\times4$ down-type quark mass matrix where the weak phase is generated minimally. $Z \bar b b$ vertex will modify in presence of the extra vector-like down-type quark. From the experimental lower bound of the partial decay width $Z\to \bar b b$ we find out the lower bound of the additional down-type quark mass. Tree level flavor changing neutral current appears in this model due to the presence of the extra vector-like down-type quark. We give the range of values of the mass splitting $\Delta m_{B_q}$ in $B^0_q-{\bar B}^0_q$ system using SM box, $Z$ mediating tree level and $Z$ mediating one loop diagrams together for both $q=d, s$. We find out the analytical expression for $\Gamma_{12}^q$ in this model from standard box, $Z$ and Higgs mediated penguin diagrams for $B^0_q-{\bar B}^0_q$ system, $q=d,s$. From this we numerically evaluate the decay width difference $|\Delta\Gamma_{B_q}/\Gamma_{B_q}|$. We also find out the numerical values of the CP asymmetry parameters $a_J$ and $a_\pi$ for the decays $B^0_d\to J/\psi K_s$ and $B^0_d\to \pi^+ \pi^-$ respectively. We get the lower bound of the scale $V$ through the upper bound of the strong CP phase.Comment: 20 pages, no figures New materials and references have been added. Text has been modified. To be appear in J.Phys.

Epidermal Langerhans Cells Rapidly Capture and Present Antigens from C-Type Lectin-Targeting Antibodies Deposited in the Dermis

Antigen-presenting cells can capture antigens that are deposited in the skin, including vaccines given subcutaneously. These include different dendritic cells (DCs) such as epidermal Langerhans cells (LCs), dermal DCs, and dermal langerin+ DCs. To evaluate access of dermal antigens to skin DCs, we used mAb to two C-type lectin endocytic receptors, DEC-205/CD205 and langerin/CD207. When applied to murine and human skin explant cultures, these mAbs were efficiently taken up by epidermal LCs. In addition, anti-DEC-205 targeted langerin+ CD103+ and langerin− CD103− mouse dermal DCs. Unexpectedly, intradermal injection of either mAb, but not isotype control, resulted in strong and rapid labeling of LCs in situ, implying that large molecules can diffuse through the basement membrane into the epidermis. Epidermal LCs targeted in vivo by ovalbumin-coupled anti-DEC-205 potently presented antigen to CD4+ and CD8+ T cells in vitro. However, to our surprise, LCs targeted through langerin were unable to trigger T-cell proliferation. Thus, epidermal LCs have a major function in uptake of lectin-binding antibodies under standard vaccination conditions

SUSY parameter determination at the LHC using cross sections and kinematic edges

We study the determination of supersymmetric parameters at the LHC from a global fit including cross sections and edges of kinematic distributions. For illustration, we focus on a minimal supergravity scenario and discuss how well it can be constrained at the LHC operating at 7 and 14 TeV collision energy, respectively. We find that the inclusion of cross sections greatly improves the accuracy of the SUSY parameter determination, and allows to reliably extract model parameters even in the initial phase of LHC data taking with 7 TeV collision energy and 1/fb integrated luminosity. Moreover, cross section information may be essential to study more general scenarios, such as those with non-universal gaugino masses, and distinguish them from minimal, universal, models.Comment: 22 pages, 8 figure

Measuring tau-polarisation in Neutralino2 decays at the LHC

We show how the sum of the two average tau polarisations in the decay chain chi20 -> stau1 tau -> tau tau chi10 in minimal supersymmetry with conserved R-parity can be measured at the LHC. This is accomplished by exploiting the polarisation dependence of the visible di-tau mass spectrum. Such a measurement provides information on the couplings of the involved SUSY particles and allows a more precise determination of the di-tau mass endpoint. If different tau decay modes can be distinguished, the polarisation and endpoint measurement can be improved even further.Comment: 16 pages, 9 figures, minor change

Likelihood analysis of the pMSSM11 in light of LHC 13-TeV data

We use MasterCode to perform a frequentist analysis of the constraints on a phenomenological MSSM model with 11 parameters, the pMSSM11, including constraints from ∼36 /fb of LHC data at 13 TeV and PICO, XENON1T and PandaX-II searches for dark matter scattering, as well as previous accelerator and astrophysical measurements, presenting fits both with and without the (g−2)μ constraint. The pMSSM11 is specified by the following parameters: 3 gaugino masses M1,2,3 , a common mass for the first-and second-generation squarks mq~ and a distinct third-generation squark mass mq~3 , a common mass for the first-and second-generation sleptons mℓ~ and a distinct third-generation slepton mass mτ~ , a common trilinear mixing parameter A, the Higgs mixing parameter μ , the pseudoscalar Higgs mass MA and tanβ . In the fit including (g−2)μ , a Bino-like χ~01 is preferred, whereas a Higgsino-like χ~01 is mildly favoured when the (g−2)μ constraint is dropped. We identify the mechanisms that operate in different regions of the pMSSM11 parameter space to bring the relic density of the lightest neutralino, χ~01 , into the range indicated by cosmological data. In the fit including (g−2)μ , coannihilations with χ~02 and the Wino-like χ~±1 or with nearly-degenerate first- and second-generation sleptons are active, whereas coannihilations with the χ~02 and the Higgsino-like χ~±1 or with first- and second-generation squarks may be important when the (g−2)μ constraint is dropped. In the two cases, we present χ2 functions in two-dimensional mass planes as well as their one-dimensional profile projections and best-fit spectra. Prospects remain for discovering strongly-interacting sparticles at the LHC, in both the scenarios with and without the (g−2)μ constraint, as well as for discovering electroweakly-interacting sparticles at a future linear e+e− collider such as the ILC or CLIC

Enhancing tumor specific immune responses by transcutaneous vaccination.

Our understanding of the involvement of the immune system in cancer control has increased over recent years. However, the development of cancer vaccines intended to reverse tumor-induced immune tolerance remains slow as most current vaccine candidates exhibit limited clinical efficacy. The skin is particularly rich with multiple subsets of dendritic cells (DCs) that are involved to varying degrees in the induction of robust immune responses. Transcutaneous administration of cancer vaccines may therefore harness the immune potential of these DCs, however, this approach is hampered by the impermeability of the stratum corneum. Innovative vaccine formulations including various nanoparticles, such as liposomes, are therefore needed to properly deliver cancer vaccine components to skin DCs. Areas covered: The recent insights into skin DC subsets and their functional specialization, the potential of nanoparticle-based vaccines in transcutaneous cancer vaccination and, finally, the most relevant clinical trial advances in liposomal and in cutaneous cancer vaccines will be discussed. Expert commentary: To define the optimal conditions for mounting protective skin DC-induced anti-tumor immune responses, investigation of the cellular and molecular interplay that controls tumor progression should be pursued in parallel with clinical development. The resulting knowledge will then be translated into improved cancer vaccines that better target the most appropriate immune players.journal articlereviewresearch support, non-u.s. gov't2017 11importe

Bayesian Fit of Exclusive b→sℓˉℓb \to s \bar\ell\ell Decays: The Standard Model Operator Basis

We perform a model-independent fit of the short-distance couplings $C_{7,9,10}$ within the Standard Model set of $b\to s\gamma$ and $b\to s\bar\ell\ell$ operators. Our analysis of $B \to K^* \gamma$, $B \to K^{(*)} \bar\ell\ell$ and $B_s \to \bar\mu\mu$ decays is the first to harness the full power of the Bayesian approach: all major sources of theory uncertainty explicitly enter as nuisance parameters. Exploiting the latest measurements, the fit reveals a flipped-sign solution in addition to a Standard-Model-like solution for the couplings $C_i$. Each solution contains about half of the posterior probability, and both have nearly equal goodness of fit. The Standard Model prediction is close to the best-fit point. No New Physics contributions are necessary to describe the current data. Benefitting from the improved posterior knowledge of the nuisance parameters, we predict ranges for currently unmeasured, optimized observables in the angular distributions of $B\to K^*(\to K\pi)\,\bar\ell\ell$.Comment: 42 pages, 8 figures; v2: Using new lattice input for f_Bs, considering Bs-mixing effects in BR[B_s->ll]. Main results and conclusion unchanged, matches journal versio

A Profile Likelihood Analysis of the Constrained MSSM with Genetic Algorithms

The Constrained Minimal Supersymmetric Standard Model (CMSSM) is one of the simplest and most widely-studied supersymmetric extensions to the standard model of particle physics. Nevertheless, current data do not sufficiently constrain the model parameters in a way completely independent of priors, statistical measures and scanning techniques. We present a new technique for scanning supersymmetric parameter spaces, optimised for frequentist profile likelihood analyses and based on Genetic Algorithms. We apply this technique to the CMSSM, taking into account existing collider and cosmological data in our global fit. We compare our method to the MultiNest algorithm, an efficient Bayesian technique, paying particular attention to the best-fit points and implications for particle masses at the LHC and dark matter searches. Our global best-fit point lies in the focus point region. We find many high-likelihood points in both the stau co-annihilation and focus point regions, including a previously neglected section of the co-annihilation region at large m_0. We show that there are many high-likelihood points in the CMSSM parameter space commonly missed by existing scanning techniques, especially at high masses. This has a significant influence on the derived confidence regions for parameters and observables, and can dramatically change the entire statistical inference of such scans.Comment: 47 pages, 8 figures; Fig. 8, Table 7 and more discussions added to Sec. 3.4.2 in response to referee's comments; accepted for publication in JHE